Estrogen deficiency induces bone loss through the gut microbiota.

Postmenopausal osteoporosis is a common bone metabolic disease, and gut microbiota (GM) imbalance plays an important role in the development of metabolic bone disease. Here, we show that ovariectomized mice had high levels of lipopolysaccharide in serum and gut microbiota dysbiosis through increases in luminal Firmicutes:Bacteroidetes ratio. We depleted the GM through antibiotic treatment and observed improvements in bone mass, bone microstructure, and bone strength in ovariectomized mice.

Nesfatin-1 suppresses autophagy of chondrocytes in osteoarthritis via remodeling of cytoskeleton and inhibiting RhoA/ROCK signal pathway.

Autophagy and cytoskeleton integrity of chondrocytes are a considered as major factors in the progression of osteoarthritis (OA) involving excessive chondrocyte apoptosis and senescence. Nesfatin-1, an adipokine, has been reported to be closely related to cell autophagy and cytoskeleton malfunction. Our previous study found that nesfatin-1 was highly correlated with OA progress in OA patient, and the expression of nesfatin-1 rises in knee articular tissue, serum and chondrocytes.

Bone mass loss in chronic heart failure is associated with sympathetic nerve activation.

Purpose: Chronic heart failure causes osteoporosis, but the mechanism remains unclear. The sympathetic nerve plays an important role in both bone metabolism and cardiovascular function.

Methods: Thirty-six adult male SD rats were randomly divided into the following four groups: sham surgery (Sham) group, guanethidine (GD) group, abdominal transverse aorta coarctation-induced heart failure + normal saline (TAC) group, and TAC + guanethidine (TAC + GD) group.

Single-intraosseous simvastatin injection suppresses cancers via activating CD8 T cells.

Immunotherapies provide effective strategies for cancer treatment. Cholesterol induces CD8 T cell exhaustion, which inhibits antitumor immunity. CD8 T cells are derived from bone marrow and transport and function in bone marrow, where provides more porous cavities for drugs to access the circulation than other solid organs.

Constitutive bone marrow adipocytes suppress local bone formation.

BM adipocytes (BMAd) are a unique cell population derived from BM mesenchymal progenitors and marrow adipogenic lineage precursors. Although they have long been considered to be a space filler within bone cavities, recent studies have revealed important physiological roles in hematopoiesis and bone metabolism. To date, the approaches used to study BMAd function have been confounded by contributions by nonmarrow adipocytes or by BM stromal cells.

Lipolysis of bone marrow adipocytes is required to fuel bone and the marrow niche during energy deficits.

To investigate roles for bone marrow adipocyte (BMAd) lipolysis in bone homeostasis, we created a BMAd-specific Cre mouse model in which we knocked out adipose triglyceride lipase (ATGL, gene). BMAd- mice have impaired BMAd lipolysis, and increased size and number of BMAds at baseline. Although energy from BMAd lipid stores is largely dispensable when mice are fed ad libitum, BMAd lipolysis is necessary to maintain myelopoiesis and bone mass under caloric restriction.

Poly(N-Isopropylacrylamide) Based Electrically Conductive Hydrogels and Their Applications.

Poly(N-isopropylacrylamide) (PNIPAM) based electrically conductive hydrogels (PNIPAM-ECHs) have been extensively studied in recent decades due to their thermal-responsive (leading to the volume change of hydrogels) and electrically conductive performance. The incorporation of conductive components into the PNIPAM hydrogel network makes it become conductive hydrogel, and as a result, the PNIPAM hydrogel could become sensitive to an electrical signal, greatly expanding its application. In addition, conductive components usually bring new stimuli-responsive properties of PNIPAM-based hydrogels, such as near-infrared light and stress/strain responsive properties.

Single Intraosseous Simvastatin Application Induces Endothelial Progenitor Cell Mobilization and Therapeutic Angiogenesis in a Diabetic Hindlimb Ischemia Rat Model.

Background: Endothelial progenitor cells have shown the ability to enhance neovascularization. In this study, the authors tested whether intraosseous delivery of simvastatin could mobilize endothelial progenitor cells and enhance recovery in a hindlimb ischemia model.

Methods: There are eight groups of rats in this study: normal control; type 1 diabetes mellitus control group control without drug intervention; and type 1 diabetes mellitus rats that randomly received intraosseous simvastatin (0, 0.

Long-term pretreatment with alendronate inhibits calvarial defect healing in an osteoporotic rat model.

Introduction: This study aimed to observe the effects of long-term alendronate pretreatment on the healing of osteoporotic calvarial defects, and further investigate the effect of alendronate combined with once-weekly parathyroid hormone following 12 weeks of alendronate treatment in ovariectomized rats.

Materials And Methods: Thirty 3-month-old female rats were ovariectomized, and 24 rats received alendronate for 12 weeks. Then, a critical defect was created in the calvaria of all animals.

Effect of weekly teriparatide injections on osteoporotic fracture healing: protocol for a double-blind, randomised controlled trial.

Introduction: Both animal studies and clinical trials have shown that daily parathyroid hormone administration promotes bone fracture healing. We previously found that weekly injections of the recombinant human parathyroid hormone teriparatide at a dosage of 20 μg/kg promoted tibial fracture healing to the same extent as daily injections of teriparatide at a dosage of 10 μg/kg in a rodent model. However, the effect of weekly teriparatide administration on human fracture healing is unreported.

Once-weekly parathyroid hormone combined with ongoing long-term alendronate treatment promotes osteoporotic fracture healing in ovariectomized rats.

This study examined the effect of once-weekly parathyroid hormone (PTH) combined with alendronate upon osteoporotic fracture healing after long-term alendronate anti-osteoporosis therapy. Seventy-six 12-week-old female Sprague-Dawley rats were either sham operated or bilaterally ovariectomized (OVX). Following confirmation of osteoporosis 3 months after OVX, the remaining 64 animals received alendronate therapy.

Effect of Single Versus Multiple Fractures on Systemic Bone Loss in Mice.

Systemic bone loss after initial fracture contributes to an increased risk of secondary fracture. Clinical research has revealed an association between the risk of future fracture and the number or magnitude of prior fractures. However, the change in systemic bone mass after single versus multiple fractures is unknown.

Osteogenic effects in a rat osteoporosis model and femur defect model by simvastatin microcrystals.

Simvastatin is a translational drug that may be used to induce local bone formation. In this study, simvastatin microcrystals were made by a wet media milling method, and then we verified the osteogenic effect of the microcrystals in rat ovariectomy (OVX)-induced osteoporosis and femur defect models. For the osteoporosis model, we delivered simvastatin microcrystals to the tibia with poloxamer hydrogels via an intraosseous injection.

Single-dose local intraosseous injection of simvastatin suppresses breast cancer with tumor vascular normalization.

Tumor vessels play important roles in cancer development and angiogenesis has been characterized as an essential process for tumor cell tumor growth. Our previous studies found that a single-dose local intraosseous simvastatin injection rapidly and long-termly mobilized bone marrow-derived endothelial progenitor cells to peripheral blood, promoting angiogenesis and ameliorating ischemia injury. However, whether intraosseous injection of simvastatin participates in cancer progression and the role of angiogenesis enhancement in this process remain unknown.

Incidence of and trends in hip fracture among adults in urban China: A nationwide retrospective cohort study.

Background: Hip fracture is a public health concern because of its considerable morbidity, excess mortality, great risk of disability, and high societal healthcare costs. China has the largest population of older people in the world and is experiencing rapid population aging and facing great challenges from an increasing number of hip fractures. However, few studies reported the epidemiology, especially at a national level.

3D printed porous titanium cages filled with simvastatin hydrogel promotes bone ingrowth and spinal fusion in rhesus macaques.

Three-dimensional (3D) printing technology can be used to manufacture implants with individualized external shapes, internal porous structures and elastic moduli similar to those of natural bone, although such implants lack biological activity. Here, we developed a porous titanium cage by electron beam melting that was filled with simvastatin/poloxamer 407 hydrogel and evaluated bone ingrowth and spinal fusion. Six adult male rhesus macaques underwent interbody fusion of the L3/4 (cage without simvastatin or hydrogel), L4/5 (cage with 0.

Short-term caloric restriction induced bone loss in both axial and appendicular bones by increasing adiponectin.

Caloric restriction (CR) is well described and has received extensive attention for its multiple benefits, including longevity and stress resistance. However, some studies have shown that CR negatively influences bone, although a mechanism hasn't been provided. Adiponectin, an adipocyte-derived hormone, can affect bone metabolism by various pathways.

Single Intraosseous Injection of Simvastatin Promotes Endothelial Progenitor Cell Mobilization, Neovascularization, and Wound Healing in Diabetic Rats.

Background: This study explored the effect of a single local intraosseous application of a small dose of simvastatin on the wound healing process in type 1 diabetic rats and related mechanisms.

Methods: The authors chose the streptozotocin-induced type 1 diabetic rat to establish a full-thickness dermal wound using a 12-mm-diameter sterile disposable punch. The rats (n = 32) were divided randomly into four groups: (1) normal control rats, (2) type 1 diabetic rats with intraosseous injection of hydrogel vehicle, (3) type 1 diabetic rats with intraosseous injection of simvastatin (0.

Comparison of the effects of once-weekly and once-daily rhPTH (1-34) injections on promoting fracture healing in rodents.

To compare the efficacy of once-weekly and once-daily subcutaneous injections of teriparatide (recombinant human parathyroid hormone 1-34) on fracture healing, 50 adult male Sprague-Dawley rats were subjected to a unilateral tibia fracture and received internal fixation with a Kirschner needle. Based on the injection dose and frequency, the rats were randomly divided into five groups (n = 10 each): subcutaneous injections of saline or 10 µg/kg/w, 20 µg/kg/w, 10 µg/kg/d, and 20 µg/kg/d teriparatide. Four weeks later, the rats were euthanatized, and the fractured tibiae were assessed using X-rays, dual-energy X-ray absorptiometry, micro-computed tomography, the three-point bending biomechanics test, and histology.